title: Abnormal expression of insulin-like growth factor-I receptor in hepatoma tissue and its inhibition to promote apoptosis of tumor cells.
abstract: Abnormal signaling of insulin-like growth factor I receptor (IGF-IR) is associated with hepatocellular carcinoma, but the underlying molecular mechanisms remain largely unknown. The objective of this study was to investigate IGF-IR's role as a signaling molecule, its pathological alteration in hepatoma tissues, and its effect on hepatoma cell proliferation when inhibited. As measured by immunohistochemical analysis, the incidence of hepatic IGF-IR expression in cancerous tissue was 80.0 % (24 of 30), which was significantly higher (P < 0.05) than 43.3 % (13 of 30) occurrence in the surrounding tissue and the nondetectable (0 of 30) frequency in the distal cancerous tissue. Hepatoma IGF-IR expression was correlated to the differentiation degree and not to the number or size of tumors, HBV infection, and AFP level. The in vitro IGF-IR expression in hepatoma cells was down-regulated significantly by picropodophyllin, a specific kinase inhibitor, in a time- and dose-dependent manner. Cell proliferation was inhibited through typical mechanisms of promoting apoptosis and cell cycle arrest (G2/M phase). Up-regulation of IGF-IR in hepatocarcinogenesis suggests that the down-regulation of IGF-IR expression could be a specific molecular target for hepatoma cell proliferation.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Yan
authors.forename: Xing
authors.initials: X
authors.lastname: Gu
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Ninghua
authors.initials: N
authors.lastname: Yao
authors.forename: Liwei
authors.initials: L
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Dengfu
authors.initials: D
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: C415032:picropodophyllin; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin